Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones
- Keck School of Medicine of University of Southern California, United States
Abstract
Much of the vertebrate skeleton develops from cartilage templates that are progressively remodeled into bone. Lineage tracing studies in mouse suggest that chondrocytes within these templates persist and become osteoblasts, yet the underlying mechanisms of this process and whether chondrocytes can generate other derivatives remain unclear. We find that zebrafish cartilages undergo extensive remodeling and vascularization during juvenile stages to generate fat-filled bones. Growth plate chondrocytes marked by sox10 and col2a1a contribute to osteoblasts, marrow adipocytes, and mesenchymal cells within adult bones. At the edge of the hypertrophic zone, chondrocytes re-enter the cell cycle and express leptin receptor (lepr), suggesting conversion into progenitors. Further, mutation of matrix metalloproteinase 9 (mmp9) results in delayed growth plate remodeling and fewer marrow adipocytes. Our data support Mmp9-dependent growth plate remodeling and conversion of chondrocytes into osteoblasts and marrow adipocytes as conserved features of bony vertebrates.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institute of Dental and Craniofacial Research (R35 DE027550)
- J Gage Crump
Burroughs Wellcome Fund (Postdoctoral Fellowship)
- D'Juan T Farmer
National Institute of Dental and Craniofacial Research (F31 025549)
- Dion Giovannone
National Institute of Dental and Craniofacial Research (K99 DE027218)
- Joanna Smeeton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Clifford J Rosen, Maine Medical Center Research Institute, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#20771) of the University of Southern California.
Version history
- Received: October 10, 2018
- Accepted: February 13, 2019
- Accepted Manuscript published: February 20, 2019 (version 1)
- Version of Record published: March 4, 2019 (version 2)
Copyright
© 2019, Giovannone et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones
eLife 8:e42736.
https://doi.org/10.7554/eLife.42736
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